Previous collaborations between Wake Forest University and the Nelson R. Mandela School of Medicine in Durban, South Africa have allowed a study on a unique cohort of Afrikaners using groundbreaking gene association techniques and behavioral characterizations. This collaboration has identified persons with single word identification and fluency (rapid naming) deficits and has shown relationships between these behavioral subgroups and allele markers on chromosomes 1, 15, and 6. There is also growing evidence that dyslexic readers may have neuroanatomic gray matter volume differences from control readers. However, the relationship between genotype/phenotype and gray matter volume remains unknown. This proposal aims to fill this knowledge gap by collecting neuroanatomical data on these previously genotyped and phenotyped Afrikaners using magnetic resonance imaging. We propose a voxel-based morphometry (VBM) analysis that will identify gray matter volume (GMV) differences between the genotypic and phenotypic subgroups. There is converging evidence that Brodmann's areas (BA) 37 and 19 in the extrastriate visual cortex are associated with dyslexia. Our overall hypothesis is that the Afrikaners with the dyslexia phenotype and genetic linkages on chromosomes most strongly associated with single word reading deficit will exhibit decreased GMV in the BA37 region. Furthermore, we propose that those dyslexic Afrikaners with chromosome markers most strongly associated with fluency deficits will be expected to show an additional GMV deficit in the more anterior lingual gyrus (BA19) region. Our ultimate goal is to use general linear modeling to determine the contribution of genotype and phenotype to GMV in BA37/19. This transcontinental collaborative study will be the first of its kind and will allow groundbreaking neuroanatomic linkages between the genotypic and phenotypic characterizations. Such an innovative project that combines genetic, behavioral, and neuroimaging techniques closely fits the exploratory spirit of the R21 mechanism. Dyslexia is a common neurobehavioral disorder, with reported prevalence rates of up to 10% of the population. This project would allow a greater understanding of which brain regions are involved in specific subtypes of this prevalent disorder and could have a great impact on remediation strategies, with tailoring of remediation to certain genotype and phenotype subgroups. Dyslexia is a common neurobehavioral disorder, affecting up to 10% of the population. We propose a transcontinental study of dyslexic and control readers that will correlate brain gray matter anatomy with certain gene markers (genotype) and behavioral findings (phenotype) in a well-studied group of South African Afrikaners. This project could have great impact on treatment strategies, with tailoring of treatment to certain genotype and phenotype subgroups. [unreadable] [unreadable] [unreadable]